The physical properties of drug delivery vehicles are important for the development of effective and targeted treatment options for human disease. In this review, we elucidate the role of the fundamental physical properties such as size, charge, elasticity, curvature, fluidity, and asymmetry in optimizing lipid-based drug delivery systems. These properties significantly influence the performance of such drug delivery vehicles in overcoming biological barriers, minimizing clearance, and improving cellular uptake. The optimization of physical properties is important in bridging the translational gap and achieving consistent clinical outcomes. By focusing on the fundamental physical properties, we also provide a comprehensive review that identifies remaining knowledge gaps and guides future development of lipid-based nanocarriers. This Review explores the role of fundamental physical properties, such as size, charge, elasticity, curvature, fluidity, and asymmetry, on optimizing lipid-based drug delivery systems. Knowledge gaps and guidance for the future development of lipid-based nanocarriers are also discussed.

We present Rheofluidics, a microfluidic technique that measures the frequency-dependent rheology of individual micron-scale objects. We apply oscillatory hydrodynamic stresses by flowing them through channels with modulated constrictions, and measure their deformation. Unlike bulk rheology, which measures collective properties, Rheofluidics provides heretofore unattainable measurements of individual particles. We apply Rheofluidics to discover frequency-dependent surface tension of surfactants, very high-frequency viscoelasticity of microgels and unexpected frequency-dependent bending modulus of vesicles.

Hydrogels typically deteriorate under high-salinity conditions because electrostatic screening and reduced polymer-solvent affinity suppress swelling and weaken load-bearing network connectivity. Here, we report a double-network hydrogel that strengthens while swelling in brine. Compared with its behavior in water, the network undergoes an ion-triggered topological reconfiguration upon salt exposure. The intrachain zwitterionic ion pairs open and reform as inter-network SBVI+-AMPS- bridges, increasing effective bridge density at lower polymer fraction. The hydrogel exhibits 1.63-fold tensile strength and 1.21-fold swelling ratio in 200 g/L NaCl compared to deionized water. SAXS and XPS confirm salt-induced structural homogenization and charge redistribution. Density functional theory calculations support strengthened ionic association under saline conditions between SBVI and AMPS. Free energy analysis reveals that reduced loop fraction and increased connectivity enable associative stabilization to compensate for elastic swelling penalties. Core-flooding demonstrates robust injectability in high-salinity porous rock. This mechanism provides design rules for salt-adaptive hydrogels.

The exchange of biological matter between bacterial cells drives adaptation and evolution. However, whether bacteria can exchange functional proteins remains unclear. In this work, we found that antibiotic treatment can induce vesicle-mediated horizontal protein transfer within and between bacterial species. We developed a genetic system in Escherichia coli to track transfer events and performed single-cell transcriptomic profiling on an isogenic population of bacteria. Antibiotics stimulated the differentiation of this isogenic population into distinct cell states: donor cells that activated a membrane stress response to release protein-containing vesicles and recipient cells that suppressed this response to acquire protein from their neighbors. Protein uptake enhanced the antibiotic persistence of recipient cells, revealing that vesicle exchange promotes bacterial survival during antibiotic treatment.

While PDMS-based microfluidic devices set the rapid prototyping standard, their application is limited by incompatibility with many non-polar solvents. This inability to tolerate organic solvents significantly restricts the types of materials that can be handled and/or synthesized. UV-curable photopolymers, such as NOA 81, present a promising solution to these challenges. NOA 81 enables simple, cost-effective device fabrication, but current limitations on proper fabrication protocols limit its full potential. Here, we present a well-defined, simple, single-step fabrication method for producing NOA 81 microfluidic devices that are compatible with organic solvents. This method allows for the rapid prototyping of devices using similar steps associated with PDMS. We report a rapid heat treatment step that enhances the chemical resistance to a wider range of organic solvents while also increasing the material's elastic modulus by nearly two orders of magnitude. We demonstrate how to control the channel wall wettability for producing water-in-oil-in-water double emulsions which serve as templates for microcapsules and amphiphilic polymer vesicles. This novel method, which we call "hard lithography", reduces the time needed to produce working prototypes to less than one day while expanding the range of solvents that can be used. It simplifies fabrication and enables the production of chemically resistant devices suitable for a wide array of applications.

The human antibody repertoire is a promising source for therapeutic-grade antibodies. Yet current methods for strategically mining these B cell repertoires are stymied by throughput and chain pairing considerations. This study presents advancements in fluidics and molecular biology that enable the multi-step encapsulation and capture of B cells from an immunized, humanized mouse in nanoliter sized droplets. Once singularly captured, antigen-specific B-cells can be lysed and individually manipulated via RT-PCR to splice cognate V genes and create a predominantly natively paired library. To explore the importance of these process improvements in library generation, we constructed natively-paired libraries against two therapeutically-relevant human proteins. Through deep sequencing, bioinformatics-driven screening and phage display, we selected functional, target-specific antibodies. Our findings reveal that natively paired libraries contain a higher percentage of target-specific antibodies and demonstrate enhanced potency and improved developability in both in silico and in vitro assessments relative to combinatorial library-derived antibodies. Furthermore, antibodies with native pairing show increased potency as well as improved in silico and in vitro developability compared to their randomly paired counterparts. To this end, we see this droplet microfluidic platform and its capacity to generate and facilitate the high-throughput interrogation of antigen-specific antibody repertoires as an important, orthogonal therapeutic antibody discovery approach.

RATIONALE:Yes-associated protein (YAP)-mediated fibroblast mechanoactivation is an important driver of fibrosis in idiopathic pulmonary fibrosis (IPF). OBJECTIVE:To characterize the role of ADAM with Thrombospondin motifs 14 (ADAMTS14) in YAP-mediated fibroblast mechanoactivation and pulmonary fibrosis. METHODS:We disrupted ADAMTS14 expression in primary human lung fibroblasts (HLFs) and demonstrated its role in YAP nuclear translocation and fibroblast activation. We confirmed the in vivo relevance of ADAMTS14 in an IPF patient cohort using transcriptomic studies. ADAMTS14-deficient fibroblasts were further characterized in mechanistic studies combining advanced microscopy, unbiased proteomics, and co-immunoprecipitation with functional mechanobiology assays to delineate substrate-matrix interactions. RESULTS:An unbiased siRNA screen identified ADAMTS14 as a regulator of YAP-mediated fibroblast activation and pro-fibrotic activity. Transcriptomic analyses of patient samples with fibrotic lung disease identified an ADAMTS14-expressing fibroblast population characterized by excessive collagen matrix synthesis and located within fibroblastic foci of IPF patients. Disruption of ADAMTS14 expression in IPF patient-derived HLFs reduced pro-fibrotic gene expression and attenuated the response to TGFβ. Mechanistically, we identified collagen V as a novel functionally relevant ADAMTS14 substrate essential for matrix stability. ADAMTS14-deficient fibroblasts produced an unstable extracellular matrix, leading to disorganized focal adhesions, impaired force transmission, and reduced focal adhesion-FAK-AKT signaling. CONCLUSION:We identify a novel ADAMTS14-collagen V-focal adhesion axis as a potential driver of fibroblast activation in IPF, linking extracellular proteolytic matrix remodeling to focal adhesion dynamics and YAP-mediated mechanoactivation. This feed-forward circuit provides a new mechanistic framework for pulmonary fibrosis and identifies potential novel therapeutic targets.

The full potentials of polymeric nanoparticles (NPs) in advanced applications strongly rely on the precise control of their physicochemical properties and some of them remain unexplored. Here, a facile strategy is presented to prepare polymeric NPs with tunable size, uniformity, shape and surface function in a single step by nanoprecipitation. Upon solvent exchange, the formation of NPs experiences three steps, including supersaturation, nucleation and growth. It is demonstrated that rapid mixing by microfluidics is a prerequisite to control the nanoprecipitation process and the precise control of NP size, uniformity, shape and surface function in a single step further broadens their applications. The insight on the underlying mechanism also shines light on the advancements of nanoprecipitation techniques. The review provides a systematic guideline for the rational design and one-step preparation of polymeric NPs with desired functions and optimal performances.

Generating biomaterials with controlled structure, morphology and physicochemical properties is a key enabler of modern bioengineering, with applications in areas ranging from tissue engineering to drug delivery. In this context, microgels — hydrogel particles with characteristic dimensions in the micrometre range — have become a foundational, modular and versatile platform for building biomaterials. Their design can be tailored across multiple length scales, integrating a range of scientific and engineering principles. In this Review, we focus on the power of droplet microfluidics to make materials drop by drop, and how this allows us to control and tailor the properties of microgels. We outline the basic principles of droplet microfluidics-enabled microgel fabrication and explore microfluidic strategies for the production of microgels and modulation of their physicochemical properties, extending beyond simple isotropic designs. We then review their applications, distinguishing between single microgels and their assemblies. We highlight how microgel features, such as size, porosity and modularity, enable unique opportunities in analytical chemistry, cell culture and drug delivery applications. Collective assemblies of microgels into jammed scaffolds are also discussed in the context of tissue engineering and biofabrication. Finally, we discuss current limitations in microgel fabrication and characterization, and outline emerging directions for future research in the field. Droplet microfluidics enables the precise fabrication of microgels, which are microscale hydrogel particles that serve as modular building blocks for biomaterials. This Review outlines principles of microfluidic microgel production, strategies for tailoring structure and functionality, and applications spanning drug delivery, cell culture and tissue engineering, while highlighting current challenges and future directions.

Microbes are increasingly used as living therapeutics, yet their uncontrolled dissemination in the body has remained a clinical roadblock. Physical containment remains largely unattainable owing to eventual bacteria escape. In this work, we present an implantable material that encapsulates and confines bacteria, wherein synthetically engineered microbes produce therapeutic payloads from within. We developed a hydrogel scaffold with dual mechanical features: high stiffness to regulate bacterial proliferation and high toughness to resist material fracture under physiological stress. This design achieved complete bacterial containment for 6 months and withstood multiple forms of mechanical loading that otherwise caused catastrophic material failure. By genetically engineering embedded bacteria, we endowed the material with environmental sensing and on-demand therapeutic release capabilities and demonstrated autonomous treatment in a murine prosthetic joint infection model.

Nanoprecipitation is a green and versatile method to prepare particles, especially biocompatible nanoparticles. However, the particles prepared by nanoprecipitation are mainly limited to solid particles and oil-core capsules, and the encapsulation and delivery by the particles are mainly restricted to hydrophobic cargos. Here, we demonstrate for the first time that it is feasible to prepare core-shell capsules with a single water core by one-step nanoprecipitation. When the disperse phase of polymers dissolved in tetrahydrofuran (THF) is injected into the continuous water phase at 70 degrees C, the polymers precipitate to form particles with most of them being capsules (about 80% water-core capsules and 20% solid particles), as the rapid inter-diffusion between good solvent and bad solvent allows the entrapping of water in the capsule core. Extensive experiments reveal that the capsule formation shows strong dependences on solvent, surfactant, and water temperature, and weak dependences on polymer, water content in THF, and PLA-to-PCL ratio. These results suggest that the formation of water-core capsules strongly relies on the mass transfer of water during the nanoprecipitation process. Besides hydrophobic cargos, hydrophilic cargos are for the first time successfully encapsulated in water-core capsules by one-step nanoprecipitation and the prepared water-core capsules are well suited for the delivery of hydrophilic cargos, showing broad applications.

Green oil-in-water (O/W) nanoemulsions incorporating essential oils (EOs) and food-derived compounds are gaining prominence as biopesticidal platforms that address the growing demand for sustainable agriculture, food safety, and reduced chemical inputs. These colloidal delivery systems enhance the solubility, stability, and bioefficacy of hydrophobic phytochemicals, offering an environmentally friendly alternative to conventional agrochemicals. This comprehensive review critically examines recent advances in the formulation and application of green O/W nanoemulsions for crop protection. We synthesize evidence on their pesticidal activity against a wide range of pests and phytopathogens relevant to food crop systems, including aphids, insects, fungi, bacteria, and weeds. Emphasis is placed on food-grade and biodegradable formulation components, such as biosurfactants and natural emulsifiers, as well as their implications for toxicological safety, environmental risk, and scalability. Nanoemulsions have been reported to enhance pest control relative to conventional formulations; however, the reported efficacy varies depending on the formulation composition, target organism, and application conditions. Their full potential remains underexplored in terms of field application, phytotoxicity, and impacts on nontarget organisms. Important gaps persist in addressing underrepresented targets such as plant viruses and nematodes. By integrating concepts of green chemistry, nanotechnology, and food system resilience, this review provides a forward-looking perspective on the role of green nanoemulsions in sustainable crop management. Their development aligns with the Sustainable Development Goals and offers promising solutions for integrated pest management, organic agriculture, and preharvest food safety, reinforcing the transition toward safer and more resilient food systems.

Hydrogels are widely used in biomedical interfaces, in which effective gas exchange (for example, O2, CO2) within a water-rich environment is essential. However, hydrogels show intrinsically limited air exchange efficiency, owing to the low solubility (C) and diffusivity (D) of non-polar gases in the polar water medium1. This limitation poses a substantial bottleneck in long-term applications, such as wearable health monitors2-7 and tissue engineering8-12. Existing methods13-16 to enhance air permeability suffer from poor robustness and/or an inherent trade-off between permeability and water content (for example, <50 vol%). Here we introduce a viscoelastic phase separation17 (VPS)-enabled strategy to create a non-collapsible, air-rich network in high-water-content hydrogels, achieving a record-high oxygen permeability of 185 barrer with 70 vol% water-a tenfold increase compared with pristine hydrogels. VPS, a ubiquitous phenomenon in soft matter, is used to drive hydrophobic, dry gas particles within a hydrophilic, wet medium into a thin, stable three-dimensional network. This approach allows the facile and scalable fabrication of air-permeable hydrogels across diverse chemistries and form factors. Physiological tests over a 10-day continuous wear condition confirmed their effectiveness in preventing fluid accumulation and maintaining skin health. This strategy paves the way for hydrogels in long-term biomedical applications in which efficient and sustained air exchange becomes critical.

Lipid vesicles consist of aqueous cores surrounded by a bilayer of phospholipids. Hybrid polymer-lipid vesicles incorporate both polymers and lipids, offering promising properties for developing pharmaceuticals, biosensors, and artificial cells. The hybrid vesicles can be symmetric, with two leaflets of identical compositions, or asymmetric, in with leaflets of dissimilar compositions, which can lead to dramatically altered properties. However, existing methods for producing symmetric and asymmetric hybrid vesicles often result in heterogenous compositions and sizes, making it challenging to quantify the effect of asymmetry and limiting applications. Here, we use a microfluidic approach to produce hybrid vesicles with either symmetric or asymmetric leaflets and precisely engineered compositions. We find that the vesicles with asymmetric leaflets are significantly stiffer and tougher than those with symmetric leaflets; moreover, the lateral diffusivity of lipids is greatly decreased. The structure for improved toughness consists of a stretchable lipid inner leaflet and a fully continuous polymer outer leaflet. This approach to precisely engineer asymmetric structures can be applied to hybrid vesicles composed of block copolymers and phospholipids soluble in chloroform and hexane, further expanding their applications.

Biocompatible amphiphilic nanoparticles (NPs) with tunable particle morphology and surface property are important for their applications as functional materials. However, previously developed methods to prepare amphiphilic NPs generally involve several steps, especially an additional step for surface modification, greatly hindering their largescale production and widespread applications. Here, a versatile one-step strategy is developed to prepare biocompatible amphiphilic dimer NPs with tunable particle morphology and surface property. The amphiphilic dimer NPs, which consist of a hydrophobic shellac bulb and a hydrophilic poly(lactic acid) (PLA) bulb with PLA-poly(ethylene glycol) (PEG) on the bulb surface, are prepared in a single step by controlled co-precipitation and self-assembly. Amphiphilic PLA-PEG/shellac dimer NPs demonstrate excellent tunability in particle morphology, thus showing good performances in controlling the interfacial curvature and emulsion type. In addition, temperature-responsive PLA-poly(N-isopropyl acrylamide) (PNIPAM)/shellac dimer NPs are prepared following the same method and emulsions stabilized by them show temperature-triggered response. The applications of PLA-PEG-folic acid (FA)/shellac dimer NPs for drug delivery have also been demonstrated, which show a very good performance. The strategy of preparing the dimer NPs is green, scalable, facile and versatile, which provides a good platform for the design of dimer NPs with tunable particle morphology and surface property for diverse applications.

Acoustofluidics, an interdisciplinary nexus of microfluidics and acoustics, is propelling the critical functionalities of manipulation, separation, and mixing within microscale environments. This integration leverages the accuracy of microfluidics with the manipulation capabilities of acoustics, thereby enhancing the vital sample processing steps and satisfying inquiries in experiments. To fulfill the requisites of practical application in clinical and research arenas, the evolution of acoustofluidics concentrates on accomplishing finer particle separation, instantaneous manipulation, and augmented integration capacity. Acoustofluidics has evolved into a sophisticated and versatile instrument for handling specimens and reactants, prompting a trend towards devices characterized by stable performance at elevated frequencies, programmable control, and seamless integration with auxiliary microfluidic systems. In this review, we present the latest advancements in the development of sophisticated acoustofluidic systems that enhance efficiency and enable precise modulation of performance across spatial and temporal scales, thereby extending their functionality and suitability for practical applications.

Biomolecular condensates form via macromolecular phase separation. Here, we report results from our characterization of synthetic condensates formed by phase separation of mixtures comprising two types of RNA molecules and the biocompatible polymer polyethylene glycol. Purine-rich RNAs are scaffolds that drive phase separation via heterotypic interactions. Conversely, pyrimidine-rich RNA molecules are adsorbents defined by weaker heterotypic interactions. They adsorb onto and wet the interfaces of coexisting phases formed by scaffolds. Lattice-based simulations reproduce the phenomenology observed in experiments and these simulations predict that scaffolds and adsorbents have different non-random orientational preferences at interfaces. Dynamics at interfaces were probed using single-molecule tracking of fluorogenic probes bound to RNA molecules. These experiments revealed dynamical anisotropy at interfaces whereby motions of probe molecules parallel to the interface are faster than motions perpendicular to the interface. Taken together, our findings have broad implications for designing synthetic condensates with tunable interfacial properties.